Investigations of HIV-1 pathogenesis have also been hampered by a lack of a tractable animal model: with the exception of one recent report, HIV-1 inoculations of chimpanzees do not result in immunodeficiency. When it became clear that SIV, the close primate lentivirus relative of HIV-1, induced an immunodeficiency in Asian macaques with clinical features similar to AIDS in man, SIV/HIV chimeric viruses (SHIVs) were constructed to address pathogenicity and vaccine issues related to the incorporated HIV-1 sequences. In one study the clearance of virus from the general circulation was analyzed in rhesus macaques receiving a continuous infusion of cell-free virus particles in the presence or absence of SHIV-specific antibodies. By measuring virion RNA, particle- associated p24 Gag protein and virus infectivity, we could demonstrate that the clearance of physical and infectious particles is extremely rapid in naive animals, with half-lives ranging from 13 to 16 minutes. In the presence of high-titered virus specific neutralizing antibodies, the half-life of virion RNA was considerable reduced (to 3.9-7.2 minutes), and infectious particles in the blood became undetectable. Although physical particles were eliminated extravascularly, the loss of virus infectivity in the blood reflected the combined effects of extravascular clearance and intravascular inactivation of infectivity due to antibody binding.In a second study to assess whether HIV-1 specific antibodies confer resistance against primate lentivirus infections, immunoglobulin (IgG) was purified from chimpanzees infected with several different HIV-1 strains, and passively transferred to pig- tailed macaques. These monkeys were subsequently challenged intravenously with a SHIV bearing an envelope glycoprotein derived from HIV-1 DH12, a dual-tropic primary virus isolate. We demonstrated that anti-SHIV neutralizing activity, determined in vitro using an assay measuring loss of infectivity, is the absolute requirement for antibody-mediated protection in vivo. Using an assay that measures 100% neutralization, the titer in plasma for complete protection of the SHIV-challenged macaques was in the range of 1:5 to 1:8. The HIV-1- specific neutralizing antibodies studied are able to bind to native gp120 present on infectious virus particles. Administration of non- neutralizing anti-HIV IgG neither inhibited nor enhanced a subsequent SHIV infection. - HIV vaccines, neutralizing antibody, virus clearance, passive transfer